Department of Biomedical Engineering and Division of Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Ann Biomed Eng. 2010 Jul;38(7):2346-57. doi: 10.1007/s10439-010-9993-6. Epub 2010 Mar 11.
Zebrafish is an emerging model system for cardiac conduction and regeneration. Zebrafish heart regenerates after 20% ventricular resection within 60 days. Whether cardiac conduction phenotype correlated with cardiomyocyte regeneration remained undefined. Longitudinal monitoring of the adult zebrafish heart (n = 12) was performed in terms of atrial contraction (PR intervals), ventricular depolarization (QRS complex) and repolarization (heart rated corrected QTc interval). Baseline electrocardiogram (ECG) signals were recorded one day prior to resection and twice per week over 59 days. Immunostaining for gap junctions with anti-Connexin-43 antibody was compared between the sham (n = 5) and ventricular resection at 60 days post-resection (dpr) (n = 7). Heart rate variability, QTc prolongation and J-point depression developed in the resected group but not in the sham. Despite a trend toward heart rate variability in response to ventricular resection, the differences between the resected and sham fish were, by and large, statistically insignificant. At 10 dpr, J-point depression was statistically significant (sham: -0.179 +/- 0.061 mV vs. ventricular resection: -0.353 +/- 0.105 mV, p < 0.01, n = 7). At 60 days, histology revealed either cardiomyocyte regeneration (n = 4) or scar tissues (n = 3). J-point depression was no longer statistically significant at 59 dpr (sham: -0.114 +/- 0.085 mV; scar tissue: -0.268 +/- 0.178 mV, p > 0.05, n = 3; regeneration: -0.209 +/- 0.119 mV, p > 0.05, n = 4). Despite positive Connexin-43 staining in the regeneration group, QTc intervals remained prolonged (sham: 325 +/- 42 ms, n = 5; scar tissues: 534 +/- 51 ms, p < 0.01, n = 3; regeneration: 496 +/- 31 ms, p < 0.01, n = 4). Thus, we observed delayed electric repolarization in either the regenerated hearts or scar tissues. Moreover, early regenerated cardiomyocytes lacked the conduction phenotypes of the sham fish.
斑马鱼是心脏传导和再生的新兴模型系统。在 60 天内，斑马鱼心脏在切除 20%的心室后会再生。心脏传导表型是否与心肌细胞再生相关仍未确定。对 12 条成年斑马鱼心脏（n=12）进行了纵向监测，包括心房收缩（PR 间隔）、心室去极化（QRS 复合体）和复极化（心脏校正 QTc 间隔）。在切除前一天记录基线心电图（ECG）信号，并在 59 天内每周记录两次。用抗连接蛋白 43 抗体进行的缝隙连接免疫染色在假手术组（n=5）和切除后 60 天（n=7）之间进行了比较。在切除组中出现了心率变异性、QTc 延长和 J 点压低，但在假手术组中没有。尽管心室切除后有心率变异性的趋势，但切除鱼和假鱼之间的差异在很大程度上没有统计学意义。在 10 天，J 点压低有统计学意义（假手术组：-0.179 +/- 0.061 mV 与心室切除组：-0.353 +/- 0.105 mV，p < 0.01，n=7）。在 60 天，组织学显示心肌细胞再生（n=4）或瘢痕组织（n=3）。在 59 天，J 点压低不再有统计学意义（假手术组：-0.114 +/- 0.085 mV；瘢痕组织：-0.268 +/- 0.178 mV，p > 0.05，n=3；再生：-0.209 +/- 0.119 mV，p > 0.05，n=4）。尽管再生组有阳性的连接蛋白 43 染色，但 QTc 间隔仍然延长（假手术组：325 +/- 42 ms，n=5；瘢痕组织：534 +/- 51 ms，p < 0.01，n=3；再生组：496 +/- 31 ms，p < 0.01，n=4）。因此，我们观察到在再生的心脏或瘢痕组织中存在延迟的电复极。此外，早期再生的心肌细胞缺乏假手术鱼的传导表型。
